Paget's disease and giant cell tumor of bone are diseases of unknown etiology in which there is a proliferation of osteoclasts or osteoclast-like cells. The osteoclasts in Paget's disease and the neoplastic cell in giant cell tumors frequently contain structures which bear a striking morphological resemblance to paramyxovirus nucleocapsids. In this project we attempt to identify the viral nature of these structures and propose experiments to rescue the putative virus. Direct and indirect immunofluorescence tests for measles, mumps, rubella and respiratory syncytial virus antigen will be performed on sections of Pageticb one, giant cell tumors and short term cultures derived from specimens from both diseases. Because of evidence that circulating mononuclear cells may be precursors to osteoclasts, circulating monocytes and monocyte cultures from Paget's patients will be tested for viral antigen, also. Ultrastructural localization of viral antigen will be performed using the immunoperoxidase technique on Pagetic bone and monocytes, giant cell tumors and short term cultures of these specimens. Virus-specific complementary DNA probes of high specific activity will be used in "in solution" molecular hybridization experiments to identify measles-virus related genetic information in specimens from Paget's disease and giant cell tumors. Using similar probes, "in situ" hybridization experiments will identify cells containing virus information and aid in the cellular localization of the viral nucleotide sequences. Further, we shall attempt to rescue the putative cryptic virus(es) by cell-fusion and co-cultivation experiments, hybridizing short term cell lines from Paget's specimens and giant cell tumors with cells permissive for viral replication.